Authors: Xueling Ou Shaohui Cai Peng Liu Jun Zeng Yuwen He Xinyao Wu Jun Du
Publish Date: 2007/10/02
Volume: 134, Issue: 5, Pages: 525-533
Abstract
Dendritic cell DCbased cancer vaccines are currently being evaluated as novel antitumor vaccination strategies but in some cases they are demonstrated to have poor clinical efficacies than anticipated A potential reason is immune tolerance due to the immunosuppressive enzyme indoleaminepyrrole 23dioxygenase IDO The aim of this study was to determine whether blocking the activity of IDO might improve the antitumor efficacy of DC/Lewis lung carcinoma LLC fusion vaccine applied to the mouse LLC modelTo prepare the DC/LLC fusion vaccine DCs were fused with LLC using polyethylene glycol PEG as described The IDO expression in the DC/LLC fusion vaccine and in the vaccinated mice was detected by western blot WB and/or immunohistochemical IHC analysis This fusion vaccine as a single agent or in combination with 1methyltryptophan 1MT an IDO inhibitor was administered to LLC mice The antitumor efficacy in different treatment was determined by regular observation of tumor development and the level of splenic cytotoxic T lymphocyte CTL response which was examined by lactate dehydrogenase LDH releaseIn the LLC mice we observed that IDOpositive cells were extensively accumulated in tumor draining lymph nodes TDLNs Furthermore WB and IHC analysis results showed that vaccination with fusion DC/LLC cells alone caused significant upregulation of IDO in spleens 1MT enhanced the antitumor efficacy elicited by DC/LLC fusion vaccine via delaying the tumor development and inducing stronger splenic CTL responses
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